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Expression of cation chloride cotransporter (NKCC1/KCC2) in brain tissue of children with focal cortical dysplasia type Ⅱ

Zhonghua Bing Li Xue Za Zhi. 2022 Nov 8;51(11):1123-1128. doi: 10.3760/cma.j.cn112151-20220418-00300.

ABSTRACT

Objective: To investigate the expression of cation chloride cotransporter (NKCC1/KCC2) in the neurons from cerebral lesions of children with focal cortical dysplasia (FCD) type Ⅱ, to provide a morphological basis for revealing the possible mechanism of epilepsy. Methods: Eight cases of FCD type Ⅱ diagnosed at Beijing Haidian Hospital, Beijing, China and 12 cases diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from February 2017 to December 2019 were included. The expression of NKCC1 and KCC2 in FCD type Ⅱa and FCD type Ⅱb was detected using immunohistochemistry and double immunohistochemical stains. The average optical density of NKCC1 in dysmorphic neurons and normal neurons was also determined using immunohistochemical staining in FCD type Ⅱa (10 cases). Results: The patients were all younger than 14 years of age. Ten cases were classified as FCD type IIa, and 10 cases as FCD type Ⅱb. NKCC1 was expressed in the cytoplasm of normal cerebral cortex neurons and KCC2 expressed on cell membranes. In dysmorphic neurons of FCD type Ⅱa, expression of NKCC1 increased, which was statistically higher than that of normal neurons (P<0.01). Aberrant expression of KCC2 in dysmorphic neurons was also noted in the cytoplasm. In the FCD Ⅱb type, the expression pattern of NKCC1/KCC2 in dysmorphic neurons was the same as that of FCD type Ⅱa. The aberrant expression of NKCC1 in balloon cells was negative or weakly positive on the cell membrane, while the aberrant expression of KCC2 was absent. Conclusions: The expression pattern of NKCC1/KCC2 in dysmorphic neurons and balloon cells is completely different from that of normal neurons. The NKCC1/KCC2 protein-expression changes may affect the transmembrane chloride flow of neurons, modify the effect of inhibitory neurotransmitters γ-aminobutyric acid and increase neuronal excitability. These effects may be related to the occurrence of clinical epileptic symptoms.

PMID:36323541 | DOI:10.3760/cma.j.cn112151-20220418-00300

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Cumulative Alcohol Consumption Burden and the Risk of Stroke in Young Adults: A Nationwide Population-Based Study

Neurology. 2022 Nov 2:10.1212/WNL.0000000000201473. doi: 10.1212/WNL.0000000000201473. Online ahead of print.

ABSTRACT

BACKGROUND: s: Alcohol consumption is one of the important modifiable risk factors for stroke in young adults. The association between the cumulative burden of alcohol consumption and its impact on incident stroke in young adults is unknown. We aimed to investigate the association between cumulative alcohol burden and the risk for stroke among young adults.

METHODS: Using data from the Korean National Health Insurance Service database, subjects between 20 and 39 years of age, who underwent 4 consecutive annual health examinations between 2009 and 2012, were included. The cumulative alcohol burden score of moderate to heavy drinking was evaluated by assigning a score of 1 for alcohol consumption ≥105 g/week at the health examination each year and calculating the sum of 4 years (0 to 4). Main outcome was incident stroke and its subtypes, ischemic stroke and hemorrhagic stroke during the follow-up period.

RESULTS: Of 1 536 668 subjects (mean age of 29.5 years, male of 71.5%, median follow-up of 6-year), 3 153 experienced an incident stroke (incidence rate, 0.37 per 1000 person-years). After multivariable adjustment, subjects with alcohol burden scores of 2, 3, and 4, who consumed more than 105 g/week of alcohol for 2, 3, and 4 years, demonstrated significantly higher risks for stroke (Hazard ratio [HR] 1.19, 95% Confidence interval [CI] 1.05-1.34 for 2; HR 1.22, 95% CI 1.09-1.38 for 3; HR 1.23, 95% CI 1.10-1.38 for 4) compared to those with a burden score of 0. This positive dose-response relationship was primarily driven by hemorrhagic rather than ischemic stroke. High alcohol burden scores (i.e., 2, 3, and 4) were significantly associated with higher risks for hemorrhagic stroke (HR 1.30, 95% CI 1.10-1.54 for 2; HR 1.42, 95% CI 1.21-1.67 for 3; HR 1.36, 95% CI 1.16-1.59 for 4) compared to a burden score of 0.

CONCLUSIONS: Young adults who engaged in moderate to heavy drinking demonstrated a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.

PMID:36323515 | DOI:10.1212/WNL.0000000000201473

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Investigating the association between income inequality in youth and deaths of despair in Canada: a population-based cohort study from 2006 to 2019

J Epidemiol Community Health. 2022 Nov 2:jech-2022-219630. doi: 10.1136/jech-2022-219630. Online ahead of print.

ABSTRACT

BACKGROUND: Deaths due to suicide, drug overdose and alcohol-related liver disease, collectively known as ‘deaths of despair’, have been markedly increasing since the early 2000s and are especially prominent in young Canadians. Income inequality has been linked to this rise in deaths of despair; however, this association has not yet been examined in a Canadian context, nor at the individual level or in youth. The study objective was to examine the association between income inequality in youth and deaths of despair among youth over time.

METHODS: We conducted a population-based longitudinal study of Canadians aged 20 years or younger using data from the Canadian Census Health and Environment Cohorts. Baseline data from the 2006 Canadian Census were linked to the Canadian Vital Statistics Database up to 2019. We employed multilevel survival analysis models to quantify the association between income inequality in youth and time-to deaths of despair.

RESULTS: The study sample included 1.5 million Canadians, representing 7.7 million Canadians between the ages of 0 and 19 at baseline. Results from the weighted, adjusted multilevel survival models demonstrated that income inequality was associated with an increased hazard of deaths of despair (adjusted HR (AHR) 1.35; 95% CI 1.04 to 1.75), drug overdose (AHR 2.38; 95% CI 1.63 to 3.48) and all-cause deaths (AHR 1.10; 95% CI 1.04 to 1.18). Income inequality was not significantly associated with suicide deaths (AHR 1.23, 95% CI 0.93 to 1.63).

CONCLUSION: The results show that higher levels of income inequality in youth are associated with an increased hazard of all-cause death, deaths of despair and drug overdose in young Canadians. This study is the first to reveal the association between income inequality and deaths of despair in youth and does so using a population-based longitudinal cohort involving multilevel data. The results of this study can inform policies related to income inequality and deaths of despair in Canada.

PMID:36323502 | DOI:10.1136/jech-2022-219630

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Characterising collateral vessels in eyes with branch retinal vein occlusions using widefield swept-source optical coherence tomography angiography

Br J Ophthalmol. 2022 Nov 2:bjophthalmol-2021-320356. doi: 10.1136/bjo-2021-320356. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: To characterise the morphology, location and functional significance of both macular and extramacular collateral vessels (CVs) in patients with a history of branch retinal vein occlusion (BRVO) using widefield swept-source optical coherence tomography angiography (WF SS OCTA).

METHODS: Patients with a history of BRVO underwent WF SS OCTA testing to acquire 12×12 mm images, which were evaluated for CVs and non-perfusion area (NPA). Region of interest analysis of individual CVs was performed to identify correlations between CV size, depth and retinal location. Mixed effects multivariate regression analyses of factors associated with NPA and visual acuity (VA) were performed.

RESULTS: Fifty-five CVs were identified in 28 BRVO eyes from 27 patients. CVs were identified in 42.9% (12/28) of eyes with a history of BRVO, and of these, 45.5% (25/55) were extramacular. The majority of CVs (87.3%, 48/55) coursed through both the superficial and the deep capillary plexus (DCP), while a subset (12.7%, 7/55) were strictly superficial. No CVs were found to course strictly through the DCP alone. CV depth increased with distance from the optic disc (p=0.011) and CV size increased with distance from the fovea (p=0.005). There were no statistically significant associations between CVs and NPA, or between CVs and VA.

CONCLUSIONS: WF SS OCTA revealed that a large fraction of CVs that form after BRVO are extramacular, and the morphology of CVs varies as a function of retinal location. Depth-resolved study of CVs may offer valuable insights on the pathophysiological mechanisms leading to the development of macular oedema.

PMID:36323493 | DOI:10.1136/bjo-2021-320356

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Evaluation of the Disease Activity index for PSoriatic Arthritis (DAPSA) with a quick quantitative C reactive protein assay (Q-DAPSA) in patients with psoriatic arthritis: a prospective multicentre cross-sectional study

RMD Open. 2022 Nov;8(2):e002626. doi: 10.1136/rmdopen-2022-002626.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the Disease Activity index for PSoriatic Arthritis (DAPSA) based on a quick quantitative C reactive protein (qCRP) assay (Q-DAPSA) in a multicentre, prospective, cross-sectional study in patients with psoriatic arthritis (PsA).

METHODS: The assessment of prospectively recruited study patients included joint examination and patient reported outcome (PRO) measures (patient global assessment, patient pain assessment). Following, the DAPSA based on a routine laboratory CRP measurement, Q-DAPSA and clinical DAPSA (cDAPSA) were calculated. Cross-tabulations and weighted Cohen’s kappa were performed to analyse the agreement of disease activity categories. Bland-Altman plots and intraclass correlation coefficients were used to determine the agreement of numerical values regarding CRP and qCRP as well as different disease activity scores.

RESULTS: Altogether, 104 patients with PsA could be included in the statistical analysis. With Q-DAPSA, 102 of 104 (98.1%) patients achieved identical disease activity categories in comparison to DAPSA with a weighted Cohen’s kappa of 0.980 (95% CI: 0.952 to 1.000). The agreement between DAPSA and cDAPSA was slightly lower with identical disease activity categories seen in 97 of 104 (93.3%) of patients and with a weighted Cohen’s kappa of 0.932 (95% CI 0.885 to 0.980).

CONCLUSIONS: The Q-DAPSA showed an almost perfect agreement with the conventional DAPSA regarding identical disease activity categories. Thus, the Q-DAPSA can be used as a timely available disease activity score in patients with PsA with the additional benefit of CRP involvement. Consequently, the Q-DAPSA could facilitate the implementation of the treat-to-target concept in clinical routine and clinical trials.

PMID:36323487 | DOI:10.1136/rmdopen-2022-002626

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Effectiveness of subacromial injections in rotator cuff lesions: systematic review and meta-analysis protocol

BMJ Open. 2022 Nov 2;12(11):e062114. doi: 10.1136/bmjopen-2022-062114.

ABSTRACT

INTRODUCTION: Subacromial injections are therapeutic options for rotator cuff injuries, with consistent results not well established yet for each drug applied. The objective of this systematic review and meta-analysis is to analyse the effectiveness of the substances used in subacromial injections for the treatment of rotator cuff injuries and shoulder impingement syndrome, considering the functional gain and pain improvement of the shoulder.

METHODS AND ANALYSIS: Beginning in November 2022, we will perform a detailed search using the MEDLINE/PubMed, EMBASE, Cochrane Central Register of Controlled Trials and LILACS databases. Relevant grey literature (reference lists, conference abstracts and academic papers) will also be included.Two reviewers will independently screen and extract the information from the literature. Bias and quality of the included studies will be evaluated using the risk of bias assessment tool provided by the Cochrane Collaboration. Statistical analyses will be performed using Review Manager V.5.4 software.

ETHICS AND DISSEMINATION: Approval and patient informed consent are not required because we will only include published literature. The results of this research will be disseminated in a peer-reviewed journal and likely through other scientific events.

PROSPERO REGISTRATION NUMBER: CRD42020199292.

PMID:36323483 | DOI:10.1136/bmjopen-2022-062114

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Study protocol for a randomised controlled trial of an e-health stepped care approach for the treatment of internet use disorders versus a placebo condition: the SCAPIT study

BMJ Open. 2022 Nov 2;12(11):e061453. doi: 10.1136/bmjopen-2022-061453.

ABSTRACT

INTRODUCTION: Excessive internet use can lead to problems for some individuals. The WHO has introduced Gaming Disorder in the International Classification of Diseases-11 (ICD-11). Previous research has shown that other internet applications can cause serious mental health problems as well. It is important to provide measures of prevention, early intervention and therapy for internet use disorders (IUDs).

METHODS AND ANALYSIS: The study ‘Stepped Care Approach for Problematic Internet use Treatment’ is a randomised, two-arm, parallel-group, observer-blind trial. The aim of the study is to investigate if a stepped care approach is effective to reduce symptom severity for IUD. The sample is primarily recruited online with a focus on employees in companies with support of health insurances. After screening, the stepped care approach depends on the success of the previous step-that is, the successful reduction of criteria-and comprise: (1) app-intervention with questionnaires and feedback, (2) two telephone counsellings (duration: 50 min) based on motivational interviewing, (3) online therapy over 17 weeks (15 weekly group sessions, eight individual sessions) based on cognitive-behavioural therapy. A follow-up is conducted after 6 months. A total of 860 participants will be randomised. Hierarchical testing procedure is used to test the coprimary endpoints number of Diagnostic and Statistical Manual of Mental Disorders, fifth edition and ICD-11 criteria. Primary analysis will be performed with a sequential logit model.

ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committees of the Universities of Lübeck (file number: 21-068), Mainz (file number: 2021-15907) and Berlin (file number: 015.2021). Results will be reported in accordance to the CONSORT statement. If the approach is superior to the control condition, it may serve as part of treatment for IUD.

TRIAL REGISTRATION NUMBER: DRKS00025994.

PMID:36323482 | DOI:10.1136/bmjopen-2022-061453

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Effectiveness of eHealth interventions targeted to improve medication adherence among older adults with mild cognitive impairment: a protocol for a systematic review and meta-analysis

BMJ Open. 2022 Nov 2;12(11):e060590. doi: 10.1136/bmjopen-2021-060590.

ABSTRACT

INTRODUCTION: Medication adherence is a vital component of successful healthcare, yet poor adherence exists, especially in older adults with mild cognitive impairment. Therefore, this study seeks to conduct a systematic review of eHealth-based interventions aimed at improving medication adherence among older adults with mild cognitive impairment.

METHODS AND ANALYSIS: An open electronic database search will be conducted in PubMed, CINAHL, PsycINFO, EMBASE and Cochrane library to identify potential studies till 2022. Two authors will independently screen the titles and abstracts, after which studies that will be eligible for full-text review will be independently assessed by two reviewers for inclusion. Studies will be selected if they evaluate eHealth interventions aiming to improve medication adherence among older adults with mild cognitive impairment. Data will be analysed by using the Comprehensive Meta-Analysis software V.3 and Review Manager (RevMan) software V.5. The authors will separately analyse each outcome measure, compute intervention effects and present them as relative risks with 95% CIs for dichotomous data. Continuous data will be presented as mean differences and standardised mean differences (if required) with 95% CIs. If substantive statistical heterogeneity is identified, we will consider the use of random-effects models that can be incorporated into the statistical analysis. We envisage that this review will adduce evidence on eHealth interventions that will improve medication adherence among older adults with mild cognitive impairment. The findings can also inform health professionals and other relevant stakeholders on current eHealth-based interventions that are used to improve medication adherence among older adults with mild cognitive impairment.

ETHICS AND DISSEMINATION: Ethical approval is not required for systematic reviews. Findings will be disseminated widely through peer-reviewed publication and at conferences.

PROSPERO REGISTRATION NUMBER: CRD42021268665.

PMID:36323471 | DOI:10.1136/bmjopen-2021-060590

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Life after COVID-19: the road from intensive care back to living – a prospective cohort study

BMJ Open. 2022 Nov 2;12(11):e062332. doi: 10.1136/bmjopen-2022-062332.

ABSTRACT

OBJECTIVES: The aim of the study was to evaluate recovery of participation in post-COVID-19 patients during the first year after intensive care unit (ICU) discharge. The secondary aim was to identify the early determinants associated with recovery of participation.

DESIGN: Prospective cohort study.

SETTING: COVID-19 post-ICU inpatient rehabilitation in the Netherlands, during the first epidemic wave between April and July 2020, with 1-year follow-up.

PARTICIPANTS: COVID-19 ICU survivors ≥18 years of age needing inpatient rehabilitation.

MAIN OUTCOME MEASURES: Participation in society was assessed by the ‘Utrecht Scale for Evaluation of Rehabilitation-Participation’ (USER-P) restrictions scale. Secondary measures of body function impairments (muscle force, pulmonary function, fatigue (Multidimensional Fatigue Inventory), breathlessness (Medical Research Council (MRC) breathlessness scale), pain (Numerical Rating Scale)), activity limitations (6-minute walking test, Patient reported outcomes measurement information system (PROMIS) 8b), personal factors (coping (Utrecht Proactive Coping Scale), anxiety and depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Global Psychotrauma Screen-Post Traumatic Stress Disorder), cognitive functioning (Checklist for Cognitive Consequences after an ICU-admission)) and social factors were used.

STATISTICAL ANALYSES: linear mixed-effects model, with recovery of participation levels as dependent variable. Patient characteristics in domains of body function, activity limitations, personal and social factors were added as independent variables.

RESULTS: This study included 67 COVID-19 ICU survivors (mean age 62 years, 78% male). Mean USER-P restrictions scores increased over time; mean participation levels increasing from 62.0, 76.5 to 86.1 at 1, 3 and 12 months, respectively. After 1 year, 50% had not fully resumed work and restrictions were reported in physical exercise (51%), household duties (46%) and leisure activities (29%). Self-reported complaints of breathlessness and fatigue, more perceived limitations in daily life, as well as personal factors (less proactive coping style and anxiety/depression complaints) were associated with delayed recovery of participation (all p value <0.05).

CONCLUSIONS: This study supports the view that an integral vision of health is important when looking at the long-term consequence of post-ICU COVID-19. Personal factors such as having a less proactive coping style or mental impairments early on contribute to delayed recovery.

PMID:36323469 | DOI:10.1136/bmjopen-2022-062332

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Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial

BMJ Open. 2022 Nov 2;12(11):e061870. doi: 10.1136/bmjopen-2022-061870.

ABSTRACT

INTRODUCTION: Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL.

METHODS AND ANALYSIS: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board.

ETHICS AND DISSEMINATION: The trial is approved by the Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access.

TRIAL REGISTRATION NUMBER: NCT04842448.

PMID:36323462 | DOI:10.1136/bmjopen-2022-061870